The Pathology Core has been highly successful in the identification of tissue changes and characterizing sites of mineral deposition as well as crystal type in three different type of human stone patients (common CaOx, intestinal bypass patients for obesity with renal stones and brushite) and the GHS rats. In the renewal, this core will oversee and conduct all morphological analyses for Projects by Lingeman and Evans using 1) light micrscopy with special stains to characterize the histopathological patterns and mineral composition of crystal deposition in our new groups of human stone formers (apatite including RTAs, primary hyperparathyroidism, ileostomy, cystinuria, uric acid stones, bariatric and CaOx with high urine pH (> pH 6.3), 2) light and transmission electron microscopic immunohistochemistry to detect the presence of a select group of known inhibitor proteins of crystal formation (osteopontin, prothombin fragment 1, fetuin-A and bikunin) in the interstitium and at the stone-plaque interface, 3) mu CT imaging to quantitate, localize and characterize mineral type of new sites of crystal deposition in whole kidneys or biopsies samples. 4) mu FTIR and electron diffraction detection techniques to identify specific sites of crystal deposition in human biopsy samples and GHS rat kidneys, 5) RT-PCR techniques to determine the presence of osteoblast-like transcripts in the interstitium of the common CaOx stone formers vs intestinal bypass or bariatric stone formers, 6) determine the mechanisms of crystal particle formation and coalescence in CaOx stone formers by quantitating particle growth/coalescence and performing double labeling, tetracyline studies to determine the rate of crystal formation, 7) provide cortical biopsy samples to Project by Coe for VDR analysis and verification of biopsy location, and 8) to assess the GHS rat for plaque formation. Project by Lingeman will supply biopsy samples from the kidney (cortex to papilla) of predetermined groups of human stone formers. Dr. Willis will perform serum and urinary lithium analyses for Project by Coe.